141 results about "Cell Maturation" patented technology

The invention discloses a neutralizing nucleic acid aptamer for targeted inhibition of a B cell activating factor and application of the neutralizing nucleic acid aptamer in treatment of systemic lupus erythematosus. The neutralizing aptamer disclosed by the invention can be used for efficiently inhibiting the combination of BAFF and specific receptors on a B cell membrane, including a BAFF receptor (BAFF-R), a human calcium regulatory cyclophilin ligand interaction molecule (TACI) and a B cell maturation antigen (BCMA), so that the proportion of plasma cells, plasma mother cells and hair growth center B cells is reduced, and finally, the generation and secretion of autoantibodies are reduced; the compound has a targeted therapeutic effect on systemic lupus erythematosus. Compared with an existing biological agent for neutralizing BAFF, the neutralizing nucleic acid aptamer has the advantages of being high in specificity, high in affinity, easy to synthesize, low in immunogenicity, low in cost, capable of being designed and programmed and the like, is a potential novel nucleic acid preparation for SLE targeted therapy, and has a good clinical transformation application prospect.

Provided herein are chimeric receptors, including chimeric antigen receptors (CARs), comprising BCMA-binding molecules, including anti-BCMA antibodies and antigen-binding fragments thereof, including heavy chain variable (VH) regions and single-chain antibody fragments, and encoding polynucleotides. In some embodiments, the anti-BCMA chimeric receptors specifically bind to BCMA. Among the anti-BCMA-binding molecules are human antibodies, including those that compete for binding to BCMA with reference antibodies, including a non-human reference antibody. Also provided are genetically engineered cells expressing the CARs and uses thereof including in adoptive cell therapy.

The invention belongs to the technical field of biology, and particularly relates to a composition for tumor targeted therapy, hydrogel and a preparation method and application thereof. The tumor targeted therapy composition provided by the invention comprises the aging tumor cells and the celecoxib, the immune activation function of the aging tumor cells is that STCs can effectively activate the maturation of dendritic cells and the immune function of T cells and NK cells, SASP of the STCs is regulated through the celecoxib, especially generation of prostaglandin E2 is inhibited, and the tumor targeted therapy effect is improved. And the combined use further enhances the anti-tumor immune effect.

Multi-specific binding proteins that bind to and kill human cancer cells are described, as well as pharmaceutical compositions and therapeutic methods useful for the treatment of cancer. The cancer can be B-cell maturation antigen (BCMA)-expressing cancer. The multi-specific binding proteins provided herein exhibit high potency and maximum lysis of target cells compared to anti-BCMA monoclonal antibodies.

The present disclosure provides methods of treating multiple myeloma in a patient in need thereof comprising administering a gamma secretase and a B-cell maturation antigen (BCMA)-directed therapy to the patient.

The disclosure concerns a method of treating cancer, especially, such as multiple myeloma, involving the combination of an anti-BCMA (B cell maturation antigen) antibody, Belantamab mafodotin -GSK2857916- and a gamma-secretase inhibitor, e.g., nirogacestat -PF03084014-. The disclosure also relates to dosages, duration of treatment and time lapses between administration of the anti-BCMA antibody and the gamma-secretase inhibitor.

The present invention relates to a complex comprising a polysaccharide conjugate, an anti-PD-L1 monoclonal antibody, and a PKM2 inhibitor. The complex of the present invention can accumulate and remain in tumor tissue, effectively stimulate dendritic cell maturation, alleviate the inhibitory immune microenvironment, and trigger a specific anti-tumor immune response. It can effectively inhibit the expression of PKM2, thereby inhibiting glycolysis in tumor tissue and providing a more favorable environment for T lymphocytes to infiltrate tumor tissue. The complex of the present invention is expected to enhance the therapeutic effect of RFA on patients with advanced HCC by reprogramming iRFA-induced tumor immunosuppression, and has great potential in improving the prognosis of patients with advanced HCC treated with RFA.

The invention relates to the field of cell biology, and particularly relates to a preparation method of a pancreatic cancer-related antigen-loaded polypeptide, which is characterized in that factors such as GM-CSF, IL-4, IFN-gamma, TNF-alpha, IL-1beta, IL-6, PGE2, Poly I: C, R848 and the like are added to promote mononuclear cells to be activated into DC cells, pancreatic cancer PANC-1, MIA PaCa-2, BxPC-3, KP4 and SW1990HM antigens are loaded, and not only is DC cell maturation promoted, but also pancreatic cancer-related antigens are loaded. The positive rate of CD83 + CD86 of the DC cells cultured by the method is 94.16%, and the secretion amount of IL-12p70 in a cell supernatant is (645.38 + / -36.49) pg / mL. By adopting the culture method disclosed by the invention, the maturation rate of the DC cells can be improved while the DC cells are activated, so that the culture method for promoting the maturation and amplification of the DC cells loaded with the pancreatic cancer antigen is achieved.

The present invention relates to antibodies, such as full-length antibodies or antigen-binding fragments thereof, that specifically bind to BCMA (B-cell maturation antigen) and CD3 (cluster of differentiation 3). The present invention also relates to antibody conjugates (e.g., antigen-drug-conjugates) comprising BCMA antibodies, compositions comprising BCMA antibodies, and methods of using BCMA antibodies and their conjugates to treat disease conditions associated with cells expressing BCMA (e.g., cancer or autoimmune diseases). The present invention further relates to heteromultimeric antibodies that specifically bind to CD3 and tumor cell antigens (e.g., bispecific antibodies that specifically bind to CD3 and BCMA). Compositions comprising such heteromultimeric antibodies, methods for preparing and purifying such heterodimeric antibodies, and their use in diagnosis and treatment are also provided.

Provided are a CAR-T cell having good blood-brain barrier permeability, a product, and a use. On the basis of the research on CAR-T cell therapy for central nervous system diseases, provided are a CAR-T cell having good blood-brain barrier permeability and a corresponding drug, for use in treating or relieving central nervous system diseases. Such a CAR-T cell uses a B cell maturation antigen as a target, and highly expresses a CXCR3 chemokine receptor and CCL1, CCL3 and CCL4 chemokines. Also provided is a product for testing and determining the blood-brain barrier permeability of the CAR-T cell, e.g., a probe, a reagent, and a kit, thereby accurately testing and determining the blood-brain barrier permeability of a certain CAR-T cell.

In a method for inducing differentiation into neuromuscular junctions according to the present disclosure, the neuromuscular junctions are induced by: preculturing human pluripotent stem cells in a medium containing activin, bFGF, a WNT signal inhibitor, a BMP signal inhibitor, and a ROCK signal inhibitor; then culturing the stem cells in a medium containing bFGF, a ROCK signal inhibitor, a WNT signal activator, and a TGFβ signal inhibitor to differentiate into neuromesodermal cells; culturing the neuromesodermal cells in a medium containing a BMP signal inhibitor, a TGFβ signal inhibitor, a retinoic acid activator, and an SHH signal activator to differentiate into skeletal muscle progenitor cells and spinal motor neuron progenitor cells in the same culture dish; and culturing these progenitor cells in a medium for cell maturation containing BDNF, GDNF, AA, and dbcAMP.

Provided are humanized nanobody targeting BCMA and a use thereof. The nanobody is capable of binding to B-cell maturation antigen (BCMA), and the isolated antigen-binding protein comprises at least one CDR in an antibody heavy chain variable region (VH). Provided are a chimeric antigen receptor, a fusion protein, a cell and a nucleic acid molecule comprising the antigen-binding protein, and a use thereof in the treatment of tumors.

Provided are a reagent combination or a kit for constructing an embryoid and the use thereof. The reagent combination or the kit can be used for inducing a stem cell to produce a blastocyst-like lineage precursor cell, a blastocyst-like cell and / or an embryoid, which are based on small-molecule induction and independent of transgenes, and have a single cell source. The produced blastocyst-like lineage precursor cell and blastocyst-like cell have a full blastocyst lineage, and are seed cells having balanced developmental competence and totipotency, which solves the problem of unbalanced cell maturation in the prior art. The produced embryoid is highly similar to natural embryos in terms of morphological characteristics and transcriptomic characteristics, has the capability of highly reproducing post-implantation embryonic development and / or gastrulation, which is beneficial for research on embryonic development in vitro. The method for inducing the stem cell to produce the blastocyst-like lineage precursor cell, the blastocyst-like cell and / or the embryoid by using the reagent combination or the kit is simple, and has high applicability and high embryoid construction efficiency.

An embodiment of the present invention relates to: a cancer antigen peptide nanostructure comprising an assembly of cancer antigen peptides conjugated with deoxycholic acid; a method for preparing same; and use thereof. The inventors of the present invention confirmed that the nanostructure of the present invention effectively stimulates the maturation of dendritic cells, migrates to lymph nodes, and activates T cells. Also, in a cancer cell model, significant infiltration of cytotoxic T lymphocytes into primary tumors was observed, and an anti-metastatic effect was confirmed. Therefore, the nanostructure according to the present invention can be effectively used as a promising immunotherapy platform that can be applied to various intractable cancers.

Provided herein are adoptive cell therapy methods involving the administration of doses of cells for treating disease and conditions, including certain plasma cell malignancy. The cells generally express recombinant receptors such as chimeric antigen receptors (CARs) specific to B-cell maturation antigen (BCMA). In some embodiments, the methods are for treating subjects with multiple myeloma (MM). Also provided are genetically engineered cells containing such BCMA-binding receptors for uses in adoptive cell therapy.

The present disclosure provides chimeric antigen receptor (CAR) molecule specific for B cell maturation antigen (BC-MA), compositions and methods for treating immune-related disorders, specifically, plasma cell pathologies such as multiple myeloma (MM).

Disclosed is a nucleic acid encoding a chimeric antigen receptor comprising an extracellular domain including an antigen recognition domain consisting of a fully human single variable heavy chain (VH) domain that binds to a first epitope on B-cell maturation antigen (BCMA), a transmembrane domain, and an intracellular domain including a signaling domain.

The present application relates to a method for preparing skeletal muscle organoids, comprising the steps of: inducing paraxial mesoderm stem cells (PMSCs) by directly differentiating human pluripotent stem cells (hPSCs); forming the paraxial mesoderm stem cells in a 3D shape, and then culturing same in a medium; inducing the proliferation of the paraxial mesoderm stem cells; and inducing the maturation of the paraxial mesoderm stem cells.

Antibodies and antigen-binding fragments thereof that bind to B cell maturation antigen (BCMA), and methods of using the same are provided.

The invention provides a composition, cell culture and application of the composition in differentiation of human pluripotent stem cells to myocardial cells and / or construction of human-derived heart organoid, and belongs to the technical field of cell engineering. The invention provides a composition. The composition comprises a fatty acid receptor antagonist, a fatty acid synthetase inhibitor and a fatty acid oxidation activator. The composition provided by the invention can regulate cell metabolism, breaks through the contradiction that the proliferation capacity and the cell maturity cannot be obtained at the same time in the traditional technology, can maintain the myocardial cells in a proliferation stage, and obtains the myocardial cells with relatively mature structures and functions, and the contractility of 3D heart organs constructed by the myocardial cells is greatly improved. The invention provides a high-quality cell source for myocardial regeneration treatment, high-throughput drug cardiotoxicity screening and heart disease mechanism research, and has remarkable clinical application value and industrialization prospect.

A B cell maturation antigen (BCMA) is expressed on plasma cells. The present invention provides methods of desensitizing a patient in need of solid organ transplantation against HLA antibodies using bispecific antibodies that bind to both BCMA and CD3 and activate T cells by the CD3 complex in the presence of plasma cells expressing BCMA. In certain embodiments, the bispecific antibodies of the invention reduce alloantibody levels and / or reduce computational population reactive antibody levels to promote solid organ transplantation and / or improve long term graft survival and / or function.

The present disclosure belongs to the fields of biotechnology and biological medicine, and specifically relates to an antibody targeting a B cell maturation antigen (BCMA) and related products thereof and medical applications. Specifically, the antibody contains a variable light chain and a variable heavy chain. The variable light chain contains a light chain complementarity-determining region (CDR) 1, a light chain CDR2, and a light chain CDR3. The light chain CDR1 has a sequence as shown in SEQ ID NO. 1, the light chain CDR2 has an amino acid sequence as shown in SEQ ID NO. 2, and the light chain CDR3 is as shown in SEQ ID NO. 3 or SEQ ID NO. 4.

The invention relates to a multi-metal element nano-aluminum adjuvant and a preparation method and application thereof, the nano-aluminum adjuvant is a nano-particle containing an aluminum element and at least one metal element selected from magnesium, zinc and calcium, the nano-particle has a layered crystal structure, and the particle size is distributed in a range of 20-2000 nm. The difunctional nano-aluminum adjuvant has the beneficial effects that the difunctional nano-aluminum adjuvant is simple and convenient in preparation method, definite in component and uniform in particle size, the particle size of the particles can be manually regulated and controlled, and the difunctional nano-aluminum adjuvant can directly promote antigen presenting cells to be mature and activated and carry out MHC-I or II type antigen presentation.

Provided herein are activated adoptive T-cell compositions targeting plasma cell dyscrasias such as multiple myeloma and methods of treating plasma cell dyscrasias such as multiple myeloma using such compositions. The T-cell compositions of the present disclosure are activated against a select group of antigens associated with multiple myeloma (MMAAs) and, in certain embodiments, in combination with more widely expressed tumor associated antigens (TAAs). In particular, the T-cell compositions of the present disclosure are directed to the MMAAs selected from B-cell maturation antigen (BCMA), X box Protein 1 (XBP1), CS1, and Syndecan-1 (CD138), or a combination thereof. In certain embodiments, the T-cell composition includes T-cells activated to a TAA selected from preferentially expressed antigen of melanoma (PRAME), Survivin, Wilms' Tumor 1 protein (WT1), and melanoma antigen 3 (MAGE-A3), or a combination thereof.

This provides a multispecific antibody that binds to BCMA. [Solution] A multispecific human heavy chain antibody (e.g., UniAb) that binds to B cell maturation antigen (BCMA). TM Disclosed are methods for producing such antibodies, compositions comprising pharmaceutical compositions containing such antibodies, and their use for treating disorders characterized by BCMA expression. In one embodiment, a multispecific antibody that binds to BCMA is provided, comprising a first binding unit comprising a variable region comprising a CDR3 sequence having at least 85% sequence identity with a specific sequence.

Provided herein are RNA sequences encoding a chimeric antigen receptor (CAR) comprising a B-cell maturation antigen (BCMA) binding molecule, along with related compositions and methods. In some embodiments, circular RNAs encoding the BCMA binding molecule or BCMA CAR, along with related compositions, methods, and precursors, are described herein. In some embodiments, these compositions comprise a transfer vehicle, e.g., comprising an ionizable lipid described herein.

The present disclosure relates to compositions and methods for treating diseases using chimeric antigen recipient cells and / or antigen binding domains that target BCMA.

The present disclosure relates to a method for treating cancer (particularly such as multiple myeloma), the method involving a combination of an anti-BCMA (B-cell maturation antigen) antibody (belantamab mafodotin - GSK2857916 -) and a γ-secretase inhibitor (such as nilotinib - PF03084014 -). The present disclosure also relates to the dosage, the duration of treatment, and the time interval between the administration of the anti-BCMA antibody and the γ-secretase inhibitor.

Provided herein are B cell maturation agent (BCMA) targeting trispecific proteins comprising a domain binding to CD3, a half-life extension domain, and a domain binding to BCMA. Also provided are pharmaceutical compositions thereof, as well as nucleic acids, recombinant expression vectors and host cells for making such BCMA targeting trispecific proteins. Also disclosed are methods of using the disclosed BCMA targeting trispecific proteins in the prevention, and / or treatment diseases, conditions and disorders.